Pain 139 (2008) 610–616

www.elsevier.com/locate/pain

Disruption of cognitive function in Fibromyalgia Syndrome q

Bruce D. Dick a,b,c,*, Michelle J. Verrier a,c, K. Troy Harker d, Saifudin Rashiq a,c
a
Department of Anesthesiology and Pain Medicine, 8-120 Clinical Sciences Building, University of Alberta, Edmonton, Alta., Canada T6G 2B7
b
Department of Psychiatry, University of Alberta, Canada
c
Multidisciplinary Pain Centre, University of Alberta Hospital, Canada
d
Department of Psychology, Dalhousie University, Canada

Received 5 February 2008; received in revised form 5 June 2008; accepted 17 June 2008

Abstract

Accumulating evidence points to significant cognitive disruption in individuals with Fibromyalgia Syndrome (FMS). This study
was carried out in order to examine specific cognitive mechanisms involved in this disruption. Standardized experimental paradigms
were used to examine attentional function and working memory capacity in 30 women with FMS and 30 matched controls. Cog-
nitive function was examined using performance on these tests and between group results were analysed in the context of important
psychological and behavioural measures. Performance of standardized everyday attentional tasks was impaired in the FMS group
compared to controls. Working memory was also found to be impaired in this group. Stimulus interference was found to be signif-
icantly worse in the FMS group as the demands of the tasks increased. These effects were found to exist independent of the measures
of mood and sleep disruption. However, when pain levels were accounted for statistically, no differences existed between groups on
cognitive measures. These findings point to disrupted working memory as a specific mechanism that is disrupted in this population.
The results of this study suggest that pain in FMS may play an important role in cognitive disruption. It is likely that many factors,
including disrupted cognition, play a role in the reduced quality of life reported by individuals with FMS.
Ó 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Keywords: Fibromyalgia Syndrome; Attention; Working memory; Cognitive disruption; Chronic pain

1. Introduction with FMS. Sleep disturbance is a common complaint in

A high proportion of individuals who suffer from
Fibromyalgia Syndrome (FMS) report cognitive deficits
that often include attention and memory dysfunction [7].
While these reports have been noted in clinical settings
for many years [13], the research literature aimed at
understanding the mechanisms underlying these prob-
lems has grown slowly. There are many factors that
could be linked to cognitive deficits noted in individuals
q
Financial support: Intramural department funding.
*
Corresponding author. Address: Department of Anesthesiology
and Pain Medicine, 8-120 Clinical Sciences Building, University of
Alberta, Edmonton, Alta., Canada T6G 2B7. Tel.: +1 780 407 1097;
fax: +1 780 407 7461.
E-mail address: bruce.dick@ualberta.ca (B.D. Dick).
FMS [31], and depression is also frequently reported
[6,16,27]. Both these factors are known to have strong
associations with cognitive disruption [14,25]. There
are also other factors that are known to play important
roles in the disruptive effects of chronic pain syndromes
including FMS such as pain-related anxiety, fear of
pain, and catastrophizing [10,11].
Importantly, a study by Park et al. strengthens the
argument that individuals with FMS do indeed experi-
ence marked cognitive disruption over and above the
effects of depression and anxiety. They also show that
these effects appear to be specific to particular cognitive
functions including memory and vocabulary deficits.
Their findings also suggest that these deficits are likely
not a result of pervasive cognitive deficits secondary to
mood disorders or other factors [21].

0304-3959/$34.00 Ó 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.pain.2008.06.017
 B.D. Dick et al. / Pain 139 (2008) 610–616
Leavitt and Katz reported another important finding
regarding the nature of cognitive deficits in FMS [17].
They noted that neurocognitive assessments and some
previous research protocols [8] have at times not found
cognitive disruption that is proportional to the reported
severity of FMS-related cognitive deficits. They pro-
posed that this variability in findings could have
occurred if different assessment protocols differentially
measured certain cognitive mechanisms. They found
that when individuals with FMS were given tests aimed
at assessing their ability to deal with stimulus competi-
tion, task performance declined markedly as stimulus
competition increased. This study was very important
as it confirmed other findings that as the cognitive load
of tasks increase, performance declines significantly in
individuals with chronic pain [5,9]. It also pointed to a
specific measure, the Auditory Consonant Trigram
(ACT), that appears highly sensitive to the cognitive
dysfunction reported by individuals with FMS.
Findings of a subsequent study in a general chronic
pain population [4] corroborate well with Leavitt and
Katz’ findings [17]. In that study, chronic pain was asso-
ciated with marked working memory disruption during
the performance of a challenging task involving stimulus
competition. Specifically, chronic pain appeared to
interfere with the formation of a memory trace during
a demanding task involving stimulus competition.
As a result, this study explored whether or not work-
ing memory disruption was associated with the decline
in performance on attentional stimulus competition
tasks in individuals with FMS using the ACT and other
measures used in recent studies [3,4,17]. We predicted
that we would find results similar to Leavitt and Katz’
[17] in that performance would decline in FMS patients
relative to matched controls on the ACT as stimulus
competition increased. We also hypothesized that per-
formance on everyday attentional tasks would be pre-
dicted by stimulus competition and working memory
decrements.
2. Methods
The University of Alberta Health Research Ethics
Board reviewed and approved this study.
2.1. Participants
Informed consent, compliant with the University of
Alberta’s Health Research Ethics Board requirements,
was obtained from all participants prior to study inclu-
sion. Based on power calculations (expected
power = 0.80) derived from previous studies [3], 30 par-
ticipants diagnosed with FMS using Wolfe’s criteria [32]
were recruited. Recruitment occurred at the Multidisci-
plinary Pain Centre at the University of Alberta Hospi-
tal and from the general public by means of campus,
611
newspaper, and public television advertisements. A
pain-free control group matched for age and gender to
the FMS group was recruited in the same manner. The
age matched control group was included to account
for the cognitive decline related to age-related factors
that have been well documented [1,21]. All participants
in the FMS group were on stable doses of medication.
Participants between ages 18 and 80 years diagnosed
with FMS and who had experienced pain for at least 6
months were recruited. Exclusion criteria included hav-
ing a medical history of significant head injury, neuro-
logical disorder, or disease known to impair
attentional function (e.g., epilepsy, Multiple Sclerosis,
Parkinson’s Disease, chronic migraine/chronic daily
headache).
2.2. Measures
Demographic: Demographic information related to
age, gender, and number of years of education was
recorded.
Medical and pain history: Medical diagnoses, etiol-
ogy, chronicity, and location were recorded along with
a detailed list of participants’ current medications.
Pain: A Numerical Rating Scale (NRS) as well as the
McGill Pain Questionnaire (MPQ) [20] were used to
measure pain intensity at the time of cognitive testing.
Participants completed the NRS by drawing a vertical
line across an 11.0 cm horizontal line to represent their
current pain level. The horizontal line was labeled at
each end with ‘‘no pain” and ‘‘worst pain imaginable”.
The MPQ provides measures of the sensory, affective,
and evaluative characteristics of pain. This question-
naire is widely used because of its ability to assess a vari-
ety of different pain characteristics, its sensitivity to
variations in pain levels, and its sensitivity to variances
in the qualities of an individual’s pain.
Attentional functioning: The Test of Everyday Atten-
tion (TEA) is a normed, standardized neuropsychologi-
cal test that measures attentional functioning in the
domains of sustained and selective attention as well as
auditory-verbal working memory. It has strong ecologi-
cal (relevance to everyday tasks) and face validity and a
short administration time. TEA subtests vary in terms of
the attentional processes assessed as well as the level of
difficulty between tasks [22].
In addition to the TEA, the ACT was also adminis-
tered [28]. This dual task paradigm required participants
to remember three item lists of consonant letters after
performing a distracter task that interfered with the con-
solidation of information into memory. This test was
administered by presenting item lists to participants
and asking them to count backwards by 3’s (dual task)
for intervals of 9, 18, or 36 s. Following this distracter
task, participants were asked to verbally report the
previously presented consonant lists. Five trials were
612 B.D. Dick et al. / Pain 139 (2008) 610–616

completed for each distracter interval. A no-distraction standardized cognitive testing. As the testing related to
condition was also included (0s delay to report). this study was extensive and time consuming (approxi-
Attentional/working memory capacity: The Reading mately 90–120 min), participants in both groups were
Span Test (RST) assesses linguistic and nonlinguistic permitted (and encouraged) to take regular rest breaks
cognitive abilities [2]. It has been proposed to reflect between subtests as needed.
basic cognitive efficiency and attentional resource capac-
ity [23]. This test was selected because it has been widely 2.4. Statistical analysis
used and validated as a measure of verbal working mem-
ory. On each trial of this test, participants were asked to An overall attentional function score was created
read a set of sentences aloud while maintaining one tar- using the sum of all TEA subtest scores as previously
get word in memory for each sentence. Five trials were reported in Dick et al. [3]. In addition, selective attention
administered at each set size, ranging from two to six and sustained attention index scores were calculated as
sentences. reported by Robertson et al. [22]. Multifactorial analy-
The RST was performed by participants using a Tos- ses of variance (MANOVAs) and stepwise multiple
hiba SatelliteTM laptop and was completed using the regressions were carried out using SPSS version 14.0.
instructions found in Daneman and Carpenter [2]. This Planned comparisons were performed using Bonferroni
paradigm also includes dual task performance as it is corrections to control for the inflation of alpha.
completed by reading each sentence out loud and then
reporting whether each sentence is grammatically cor- 3. Results
rect or not. While performing that task, participants
are also required to remember the final word of all sen- No significant differences existed between groups on
tences in the set. After each entire set, participants were measures of age (F[1,58] = 0.00, p = .984) or years of
asked to recall the last word in all the sentences in the education (F[1,58] = 1.28, p = .263). Not surprisingly,
set, preferably in the order in which they were presented. significant differences were detected between groups on
As the test progressed, task difficulty and attentional all measures of pain (all p = .000). Significant between
demand were enhanced by increasing set size from two group differences were also found on measures known
to six sentences. to be related to cognitive disruption including depres-
Two outcome scores were derived for this test. The sion (F[1,58] = 74.50, p = .000), anxiety (F[1,58] =
measure of primary interest was the total RST score 58.16, p = .000), average hours of sleep per night
for the number of words correctly remembered for the (F[1,58] = 5.36, p = .024), and night wakings
whole paradigm, a reflection of working memory func- (F[1,58] = 117.33, p = .000). In addition, groups were
tion. The second score represented participants’ accu- found to differ significantly on reported quality of life
racy at judging whether or not sentences were (F[1,58] = 255.96, p = .000). Participants’ demographic,
grammatically correct. sleep, and medical information can be found in Table
Quality of life (QOL): The 15D was used to measure 1 and questionnaire data, in Table 2.
health-related QOL. This 15-item measure assesses lim- Attentional disruption was examined using
itations in physical activities, social activities, usual role MANCOVAs with measures of depression, anxiety,
activity, general mental health (psychological distress and sleep as covariates. Significant differences were still
and well-being), vitality (energy and fatigue), and gen- found between groups where individuals with FMS per-
eral health perceptions as a result of physical and/or formed more poorly on an overall attentional score
emotional health problems. A utility score between 0
and 1 is derived from these 15 measures [26].
Mental health (anxiety and depression): The Hospital Table 1
Anxiety and Depression (HAD) scale, a brief (14-item) Demographic, sleep, and medication information for all participants
measure, was used to assess participants’ current levels Variable Fibromyalgia group Control group
of depression and anxiety [34]. M (SD) M (SD)
Sleep: Participants reported their average total hours Age (years) 49.60 (12.54) 46.56 (10.00)
of sleep per night along with their average number of Education (years) 14.17 (2.49) 15.20 (4.34)
wakings per night. Mean hours of sleep 6.58 (1.79) 7.48 (1.15)
per night
Mean number of 2.80 (1.82) 1.41 (1.11)
2.3. Procedure wakings per night
Medications
On the day of testing, the informed consent process Opioids (%) 40.00 0.00
was carried out and demographic and medical informa- NSAIDS (%) 33.33 10.00
tion was collected. All data were collected in a standard- Tricyclics (%) 46.67 6.67
Other (%) 83.33 50.00
ized manner by a research assistant trained in the use of
 B.D. Dick et al. / Pain 139 (2008) 610–616 613

Table 2 Table 3
Questionnaire data for all participants Cognitive test performance outcome means for all participants
Measure Possible Fibromyalgia Control Measure Fibromyalgia Control
group group group group
Score M (SD) M (SD) M (SD) M (SD)
range
Test of Everyday Attention (TEA)
Pain rating (NRSa) 0–10 6.52 (2.64) 0.34 (0.78) Overall score 95.07 (14.55) 106.97 (10.85)*
McGill Pain Auditory verbal 18.53 (5.37) 21.80 (4.33)**
Questionnaire (MPQb) working memory
Sensory index 0–42 27.23 (4.60) 0.00 (0.00) Selective attention 29.40 (6.08) 32.70 (5.98)
Affective index 0–14 5.40 (2.97) 0.00 (0.00) Sustained attention 27.07 (4.33) 29.70 (3.53)
Pain rating index (total) 0–78 45.77 (8.85) 0.00 (0.00)
Reading Span Test (RST)
Quality of life (15Dc) 0–1 0.64 (0.10) 0.96 (0.04)
Working memory score 47.74 (17.72) 61.83 (12.72)***
Anxiety (HADd) 0–21 9.60 (3.54) 2.97 (3.19)
Grammatical 95.43 (3.79) 96.57 (2.53)****
Depression (HADd) 0–21 8.07 (4.46) 0.80 (1.16)
judgment score
a
NRS, Numerical Rating Scale.
b Auditory Consonant
MPQ, McGill Pain Questionnaire.
c Trigram (ACT)
15D, Quality of life utility score.
d 0s 14.91 (0.29) 14.63 (0.99)
HAD, Hospital Anxiety and Depression Scale.
9s 10.35 (3.38) 12.30 (2.59)
18 s 8.74 (4.21) 10.73 (2.53)
36 s 7.26 (4.47) 10.13 (3.15)*****
derived from the TEA (F[5,54] = 4.32, p = .002), the *
p = .002.
TEA auditory verbal working memory index **
p = .006.
(F[5,54] = 3.71, p = .006), the RST score for accuracy ***
p = .001.
****
of judging whether or not sentences were grammatically p = .010.
*****
correct (F[5,47] = 3.42, p = .010), the total RST score p = .005.
for number of words correctly remembered
(F[5,47] = 5.36, p = .001), the ACT score at a delay of
36 s (F[5,47] = 3.94, p = .005), and the ACT Total Score could have played a role in at least some of these non-
(F[5,47] = 2.51, p = .043), but not at intervals of 9 significant differences.
(F[5,47] = 1.46, p = .220), or 18 s (F[5,47] = 1.48, In order to examine the effects of working memory
p = .214). TEA measures of selective and sustained function and stimulus interference on attentional func-
attention were found to be significantly worse in the tion, stepwise regressions were used (Table 5). The
FMS group using a MANOVA without the above RST score for the number of words correctly
covariates (selective: F[1,58] = 4.49, p = .038; sustained
F[1,58] = 6.65, p = .012) but were not significantly dif-
ferent when the MANCOVA was carried out (selective: Table 4
F[5,58] = 1.19, p = .329; sustained F[5,58] = 2.25, Cognitive test performance outcome means based on opioids use for
all participants in the FMS group
p = .062). When the NRS pain score was entered as a
covariate, none of the cognitive scores between groups Measure Fibromyalgia Fibromyalgia
group group
on the TEA, RST, or ACT were significantly different.
Taking opioids No opioids
Means for group results on cognitive tests can be found M (SD) M (SD)
in Table 3.
Test of Everyday
While it can be challenging to statistically account for Attention (TEA)
the effects of medication on cognitive function, a post- Overall score 101.56 (10.01) 92.29 (15.48)
hoc ANOVA was carried out to compare cognitive func- Auditory verbal 22.67 (4.39) 16.76 (4.81)*
tion between individuals with FMS who were taking working memory
Selective attention 27.89 (6.15) 30.05 (6.09)
opioids (n = 9) and those who were not (n = 21). This
Sustained attention 28.89 (3.26) 26.29 (4.56)
analysis found that the individuals taking stable doses
of opioids performed significantly better on the Audi- Reading Span Test (RST)
Working memory score 48.11 (19.48) 42.57 (16.09)
tory Verbal Working Memory Index of the TEA Grammatical judgment score 96.71 (1.98) 94.88 (4.23)
(F[1,28] = 9.99, p = .004). No statistically significant dif-
ferences were found between these subgroups on any Auditory Consonant
Trigram (ACT)
other TEA, RST, or ACT measures. However, individ- 0s 15.00 (0.01) 14.86 (0.36)
uals in the opioid subgroup performed better on average 9s 11.22 (2.24) 9.71 (3.47)
on all of those measures except on the TEA Selective 18 s 9.11 (4.05) 8.19 (4.05)
Attention Index (Table 4). It may be that a lack of sta- 36 s 8.44 (3.56) 6.38 (4.39)
tistical power due to the sample size of these subgroups *
p = .004.
614 B.D. Dick et al. / Pain 139 (2008) 610–616
Table 5
Regression values for working memory predictors of overall attentional function score
Measure B SE B
Reading Span Test (RST)
Working memory score .45 .09
Auditory Consonant Trigram (ACT)
Total score .67 .18
remembered, representing working memory function,
was a significant predictor of overall TEA attentional
function (p = .000). The ACT total score also signifi-
cantly predicted this measure of attentional function
(p = .000). The RST score for accuracy on the grammat-
ical judgment task was not a significant predictor of
attentional function.
4. Discussion
A number of very important differences were found
between groups on psychological and cognitive mea-
sures. While demographic measures were not signifi-
cantly different between groups, there was a very large
discrepancy between groups on measures related to
mood, sleep disruption, and pain. In the context of these
findings, it is not surprising that there was a dramatic
difference between groups on a measure of quality of life
where individuals in the FMS group reported signifi-
cantly reduced quality of life.
As there is a well established link between cognitive
disruption and each of depression, anxiety, and sleep
disruption, we sought to ascertain whether or not cogni-
tive dysfunction in FMS would be a primary result of
these factors rather than pain. When these factors were
statistically accounted for, the differences in cognitive
function still remained between groups. Of note, stimu-
lus competition was only disrupted when the cognitive
load associated with the ACT task was the highest. This
finding corresponds well with previous findings [5,9].
However, when pain scores were accounted for, these
differences disappeared. This provides considerable evi-
dence that chronic pain may play an important role in
the disruption of cognitive processes in FMS.
Further, our prediction that stimulus interference
and working memory disruption would have a strong
association with tasks that tapped everyday atten-
tional function was strongly borne out. Thus, it
appears that impaired working memory function is
disrupted by chronic pain. This effect was seen
between groups in this study even after assumed influ-
ential factors such as depression and sleep disruption
were accounted for. It also appears that stimulus com-
petition may be an important factor that is involved
in the process that results in observable and reported
cognitive impairment. These findings in individuals
with FMS are consistent with the previous findings
Beta t score Significance (p)
.56 5.14 .000
.45 3.78 .000
in a general chronic pain population [4] and in a
group of individuals with FMS [17].
As seen in Park et al.’s findings [21], we were able to
distinguish between global cognitive dysfunction and
specific processes involved in our findings. In this study,
working memory capacity predicted overall attentional
function. A measure associated with a complex language
processing did not predict attentional disruption. This
may be an important differential distinction from a the-
oretical perspective. One possibility for this difference
could be that despite the complexity of the language
task, the semantic processing required by the RST task
was more of an automatic cognitive process than the
working memory task of the RST. Automatic cognitive
processing has been noted previously to be less inter-
rupted by pain than controlled processing [10,11].
With regard to the limitations inherent in this study,
we acknowledge that many factors can play a role in the
effects that we have studied. In designing this study, we
endeavoured to account for a number of factors known
to play a role in cognitive function. Given the potential
that medications taken by individuals with FMS could
play a role in our findings, we attempted to carefully
record medications taken by all participants. Unfortu-
nately, it is difficult to statistically control for the effects
of these medications. Our finding that FMS participants
taking stable doses of prescribed opioids performed sig-
nificantly better on a measure of auditory verbal work-
ing memory than those with FMS not taking opioids
supports previous research. There is a strong evidence
from previous studies that cognitive function is either
not affected or it is improved in individuals taking anal-
gesics [19,29]. That our FMS subgroup taking opioids
performed better (though not statistically significantly
better) on all cognitive measures except on a measure
of selective attention suggests that further research on
this issue is warranted. It is important to be aware that
the potential effects of opioids and other medications
taken by participants on cognitive function is complex
and that further study is needed.
Further, it is recognized that testing-related increases
in pain and fatigue could play a confounding role in the
between-group differences reported here. We suggest
that such difficulties with pain and stamina are endemic
to having a chronic pain syndrome and almost surely
play a role in the functional impairments and reduced
quality of life reported by this population. However,
 B.D. Dick et al. / Pain 139 (2008) 610–616
we also suggest that such differences are a reflection of
the reality of such medical conditions and strengthen
the ecological validity of the findings reported here.
Future research could incorporate a number of shorter
testing sequences to account for differences in test-
related fatigue.
Previous research had noted an association between
memory deficits and mental clarity with poorer mental
health in individuals with FMS [14]. In that study, the
results pointed to the vulnerability of this population
to cognitive disruption. Unfortunately, these effects are
often discounted or disputed when patients present with
these complaints. Patients are often accused of malinger-
ing or exaggeration when making these reports. Our
findings suggest that these effects are real consequences
of FMS. They also suggest that this constellation of
symptoms can result in tremendous negative effects on
a person’s quality of life. Studies that have examined
the phenomenology of FMS strongly support this [12].
The accumulating evidence points to a biological sub-
strate that may be associated with cognitive function
that is significantly affected by chronic pain. The exact
nature of the biological ‘hardware’ affected by chronic
pain remains unknown. Sephton et al. have reported
that FMS and the cognitive symptoms associated with
it could be biologically related to a disorder of the neu-
roendocrine stress response [25]. There has also been a
recent suggestion that there may be evidence that cogni-
tive deficits in FMS are associated with a dysfunction of
central processing related to low arousal and impaired
filtering mechanisms [33]. Interactions between immune
and neural activities have also been investigated in indi-
viduals with FMS by Lekander and colleagues [18]. That
study found that immune system activity was associated
with cortical areas responsible for attentional function,
affect, and pain perception. Some evidence exists of dif-
ferences in brain morphology in FMS [15,24], but these
findings require further study and replication. Unfortu-
nately, much remains to be learned about the biological
mechanisms involved in this effect. The findings reported
here in addition to the broader literature that has
explored cognitive deficits in individuals with chronic
pain show a clear need for a stronger theoretical frame-
work regarding cognitive mechanisms affected by
chronic pain.
Imaging studies in FMS have noted differences in
cerebral activity including higher neural recruitment
during cognitive tasks [7,30]. Much remains to be
learned from those techniques as equipment and exper-
imental paradigms evolve and improve. Each additional
report provides information that adds a piece to the
complex puzzle of how chronic pain disrupts attention
in FMS. The accumulating evidence suggests that many
factors must be taken into account as we strive to under-
stand and treat FMS and improve the quality of life of
those with this problem.
615
Acknowledgements
We thank all the individuals who participated in this
study. We are also grateful to Peggianne MacKenzie
and Sherry Lippa in the Multidisciplinary Pain Centre
for their assistance during the recruitment phase of this
study.
No financial support or benefit related to this re-
search has been received by the authors which could cre-
ate a conflict of interest or the appearance of a potential
conflict of interest.
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